What the FDA labels say about taking them together
Methotrexate and nitrous oxide
Methotrexate's FDA label of May 27, 2026 names nitrous oxide in its drug interactions section; the nitrous oxide labels PlainMeds reads (4) do not name methotrexate. The methotrexate label: “The use of nitrous oxide anesthesia potentiates the effect of methotrexate on folate dependent metabolic pathways, resulting in the potential for increased toxicity.”
Check it at the source: the methotrexate FDA label on DailyMed (effective May 27, 2026, Accord Healthcare Inc.); the nitrous oxide FDA label on DailyMed (effective December 2, 2025, Machine & Welding Supply Company dba Arc3 Gases South).
What does the methotrexate label say about nitrous oxide?
Methotrexate label, drug interactionsOral antibiotics (including neomycin) Antifolate drugs (e.g., dapsone, pemetrexed, pyrimethamine and sulfonamides) Oral or intravenous penicillin or sulfonamide antibiotics Aspirin and other nonsteroidal anti-inflammatory drugs Highly protein-bound drugs (e.g., oral anticoagulants, phenytoin, salicylates, sulfonamides, sulfonylureas, and tetracyclines) Hepatotoxic products Proton pump inhibitors Weak acids (e.g., salicylates) Nephrotoxic products Probenecid Nitrous Oxide Coadministration of methotrexate with nitrous oxide anesthesia potentiates the effect of methotrexate on folate-dependent metabolic pathways, which may increase the risk of severe methotrexate adverse reactions.
Rasuvo label (Medexus Pharma Inc., December 15, 2025), drug interactionsNitrous oxide The use of nitrous oxide anesthesia potentiates the effect of methotrexate on folate dependent metabolic pathways, resulting in the potential for increased toxicity.
Methotrexate label (Hospira, Inc., August 22, 2025), drug interactionsHematotoxic agents Nitrous Oxide Coadministration of methotrexate with nitrous oxide anesthesia potentiates the effect of methotrexate on folate-dependent metabolic pathways, which may increase the risk of severe methotrexate adverse reactions.
Source: FDA drug label (Rasuvo, NDA205776), Medexus Pharma Inc., effective December 15, 2025 (SPL set d0075461-0e7e-4967-9c9b-d6440e912c0e), via openFDA
Source: FDA drug label (Methotrexate, NDA011719), Hospira, Inc., effective August 22, 2025 (SPL set 0e30eaef-5a09-4104-8a11-c32933eadeab), via openFDA
Source: FDA drug label (Otrexup, NDA204824), Antares Pharma, Inc., effective January 31, 2025 (SPL set 9ab8ce16-f7de-41d4-a4c8-1c742621b6d5), via openFDA
Source: FDA drug label (Methotrexate), Accord Healthcare Inc., effective May 27, 2026 (SPL set 874c7f43-a3be-4236-89cc-24c44e3c5813), via openFDA; the full label on DailyMed
What does the nitrous oxide label say about methotrexate?
Nitrous oxide's label (effective December 2, 2025) and its 3 other brand-application labels do not name methotrexate in these sections. A label lists what its studies and reports found; it is not a complete list.
Source: FDA drug label (Nitrous Oxide), Machine & Welding Supply Company dba Arc3 Gases South, effective December 2, 2025 (SPL set a5070767-c36a-4131-aa09-1bccfa24aa71), via openFDA; the full label on DailyMed
These are the labels' own sentences. PlainMeds does not grade interactions; a pharmacist or prescriber can say what they mean for one person's medicines.
Both medicines on the record
| Methotrexate | Nitrous oxide | |
|---|---|---|
| Labeled for | Rheumatoid arthritis, Psoriasis, Leukemia, lymphoma and myeloma, Breast cancer | n/a |
| Boxed warning | Yes | No |
| Pharmacy cost (NADAC) | $0.158 per tablet 2.5 mg tablet | n/a |
| Shortage now | In shortage | No current entry |
Source: FDA NDC Directory, CMS NADAC of October 7, 2026 and the FDA Drug Shortage Database (FDA files October 8, 2026)
What next?
- Check more medicines together
- up to five at once